Na+/H+ exchanger inhibition modifies dopamine neurotransmission during normal and metabolic stress conditions

Marcelo A. Rocha, David P. Crockett, Lai Yoong Wong, Jason R. Richardson, Patricia K. Sonsalla

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Na+/H+ exchanger (NHE) proteins are involved in intracellular pH and volume regulation and may indirectly influence neurotransmission. The abundant NHE isoform 1 (NHE1) has also been linked to brain cell damage during metabolic stress. It is not known, however, whether NHE1 or other NHE isoforms play a role in striatal dopamine (DA) neurotransmission under normal or metabolic stress conditions. Our study tested the hypothesis that NHE inhibition with cariporide mesilate (HOE-642) modifies striatal DA overflow and DAergic terminal damage in mice caused by the mitochondrial inhibitor malonate. We also explored the expression of NHE1-5 in the striatum and substantia nigra. Reverse microdialysis of HOE-642 elicited a transient elevation followed by a reduction in DA overflow accompanied by a decline in striatal DA content. HOE-642 pre-treatment diminished the malonate-induced DA overflow without reducing the intensity of the metabolic stress or subsequent DAergic axonal damage. Although NHE isoforms 1-5 are expressed in the striatum and midbrain, NHE1 protein was not co-located on nigrostriatal DAergic neurons. The absence of NHE1 co-location on DAergic neurons suggests that the effects of HOE-642 on striatal DA overflow are either mediated via NHE1 located on other cell types or that HOE-642 is acting through multiple NHE isoforms.

Original languageEnglish (US)
Pages (from-to)231-243
Number of pages13
JournalJournal of neurochemistry
Volume106
Issue number1
DOIs
StatePublished - Jul 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • Cariporide
  • Dopamine
  • Microdialysis
  • Na/H exchanger
  • Neurotransmission
  • Striatum

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